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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02674

Macrophage coordination of the interferon lambda immune response

 Scott A. Read1*,  Ratna Wijaya2, Mehdi Ramezani-Moghadam3, Enoch Tay4, Steve Schibeci5, Chris Liddle2,  Vincent W. Lam6, Lawrence Yuen6, Mark W. Douglas2,  David Booth2, Jacob George2 and Golo Ahlenstiel1*
  • 1Western Sydney University, Australia
  • 2University of Sydney, Australia
  • 3Centenary Institute Australia, Australia
  • 4Western Sydney Local Health District, Australia
  • 5Westmead Institute for Medical Research, Australia
  • 6Westmead Hospital, Australia

Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14+ monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes.

Keywords: macrophage, interferon lambda, innate immunity, Liver, Kupffer

Received: 02 Jun 2019; Accepted: 30 Oct 2019.

Copyright: © 2019 Read, Wijaya, Ramezani-Moghadam, Tay, Schibeci, Liddle, Lam, Yuen, Douglas, Booth, George and Ahlenstiel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Scott A. Read, Western Sydney University, Penrith, Australia, s.read@westernsydney.edu.au
Prof. Golo Ahlenstiel, Western Sydney University, Penrith, Australia, g.ahlenstiel@westernsydney.edu.au